Back to resultsAssessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
Primary Purpose
COVID-19
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Ruxolitinib
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Cytokine storm, COVID-19, ARDS, SARS-CoV-2, ruxolitinib, pneumonia
Eligibility Criteria
Inclusion Criteria:
- Participant or guardian health proxy must provide informed consent before any study assessment is performed.
- Male or female participants aged ≥ 12 years.
- Participants with coronavirus (SARS-CoV-2) infection confirmed ≤ 3 weeks prior to randomization by any test with local regulatory approval.
- Participants who are intubated and receiving mechanical ventilation due to COVID-19-associated ARDS and have a PaO2/FiO2 of ≤ 300 mmHg within 6 -hours of randomization.
Participants with lung imaging showing bilateral or diffuse pulmonary infiltrates on chest x-ray or CT scan.
Exclusion Criteria:
- Known history of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.
- Presence of severely impaired renal function defined by estimated creatinine clearance < 15 mL/min measured or calculated by Cockcroft-Gault equation or calculated by the updated bedside Schwartz equation. Participants must not be receiving CRRT or intermittent hemodialysis at screening.
- In the opinion of the investigator, unlikely to survive for > 24 hours from randomization.
- Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19).
- Currently receiving ECMO.
- Participant may not be sharing a ventilator, or co-ventilating, with any other patient.
- Treatment with anti-IL-6, IL-6R, IL-1RA, IL-1β, or GM-CSF antagonists, or a BTK inhibitor, within 7 days of randomization.
- Treatment with a JAK inhibitor within 30 days of randomization.
- Participants who are on long-term use of antirejection or immunomodulatory drugs.
- Pregnant or nursing (lactating) women.
Sites / Locations
- Honor Health Research Institute
- Sharp Memorial Hospital
- Georgetown University Hospital
- Teradan Clinical Trials
- University of Florida
- Tampa General Hospital
- University of South Florida
- Northshore University Health System
- Loyola University Medical Center
- Indiana University Simon Cancer Center
- Indiana University Health Central Indiana Cancer Centers
- East Jefferson General Hospital
- Johns Hopkins University
- Boston Medical Center
- Lahey Hospital & Medical Center
- University of Massachusetts Medical School
- Healthpartners Cancer Care Center - Regions Hospital
- Mercy Research
- Hackensack University Medical Center
- Rutgers Njms Clinical Research Unit
- Holy Name Medical Center
- University of Rochester Medical Center
- Duke University Medical Center
- East Carolina University
- University of Cincinnati
- Kettering Cancer Care
- Jefferson University Hospitals
- Temple University
- West Penn Hospital
- Allegheny Health Network
- St David'S Medical Center
- University of Texas Health Science Center At Houston - McGovern Medical School
- University of Texas Health Science Cente
- Wenatchee Valley Hospital and Clinics
- Aurora Research Institute
- Sbih City Hospital 15
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo + Standard of Care (SoC)
Ruxolitinib 5mg + Standard of Care (SoC)
Ruxolitininb 15mg + Standard of Care (SoC)
Arm Description
Matching Placebo will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Ruxolitinib 5mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Ruxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Have Died Due to Any Cause
To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.
Secondary Outcome Measures
Number of Ventilator Free Days
Number of days participant did not require mechanical ventilation
Number of ICU Free Days
Number of days participant is out of the ICU
Oxygen Free Days
Number of days participant did not receive supplemental oxygen
Vasopressor Free Days
Number of days without use of vasopressor therapy
Hospital Free Days
Number of days Partcipant is out of the hospital
Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale
Participants with at least 2-point improvement at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale
Participants with at lest 1-point improvement in clinical status at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale
TIme to improvement compared to baseline. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Percentage of Participants With the COVID-19 Ordinal Scale Reported
Clinical status of participant at Day 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Change in the COVID-19 9-point Ordinal Scale
Change in the Clinical status of participant at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Change in SOFA Score
Sequential Organ Failure Assessment (SOFA) score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each system gets a score from 0 (normal) to 4 (abnormal) and the sum of each score defines the final SOFA score, which 24 is the maximum score (high risk of morality) and 0 is the minimum score (low risk of mortality).
Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events
Treatment-emergent AEs are judged as related by the investigator or have a missing causality.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04377620
Brief Title
Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Terminated
Why Stopped
Study terminated by sponsor
Study Start Date
May 24, 2020 (Actual)
Primary Completion Date
February 26, 2021 (Actual)
Study Completion Date
February 26, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Cytokine storm, COVID-19, ARDS, SARS-CoV-2, ruxolitinib, pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Double blinded
Allocation
Randomized
Enrollment
211 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo + Standard of Care (SoC)
Arm Type
Placebo Comparator
Arm Description
Matching Placebo will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Arm Title
Ruxolitinib 5mg + Standard of Care (SoC)
Arm Type
Experimental
Arm Description
Ruxolitinib 5mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Arm Title
Ruxolitininb 15mg + Standard of Care (SoC)
Arm Type
Experimental
Arm Description
Ruxolitinib 15mg will be administered BID approximately 12 hours apart without regard to food/feeding via enteric feeding tube or oral.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo administered BID approximately 12 hours apart
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
INCB018424, Oral Jak Inhibitor
Intervention Description
Ruxolitinb administered BID approximately 12 hours apart
Primary Outcome Measure Information:
Title
Percentage of Participants Who Have Died Due to Any Cause
Description
To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.
Time Frame
Study start to Day 29
Secondary Outcome Measure Information:
Title
Number of Ventilator Free Days
Description
Number of days participant did not require mechanical ventilation
Time Frame
Study start to Day 29
Title
Number of ICU Free Days
Description
Number of days participant is out of the ICU
Time Frame
Study start to Day 29
Title
Oxygen Free Days
Description
Number of days participant did not receive supplemental oxygen
Time Frame
Study start to Day 29
Title
Vasopressor Free Days
Description
Number of days without use of vasopressor therapy
Time Frame
Study start to Day 29
Title
Hospital Free Days
Description
Number of days Partcipant is out of the hospital
Time Frame
Study start to Day 29
Title
Percentage of Participants With at Least 2-point Improvement in the COVID-19 Ordinal Scale
Description
Participants with at least 2-point improvement at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Time Frame
Study start to Days 15 and 29
Title
Percentage of Participants With at Least 1-point Improvement in the COVID-19 Ordinal Scale
Description
Participants with at lest 1-point improvement in clinical status at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Time Frame
Study start to Days 15 and 29
Title
Time to Improvement From Baseline Category to Earliest 1-point Improvement in the COVID-19 Ordinal Scale
Description
TIme to improvement compared to baseline. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Time Frame
Study Start to Day 29
Title
Percentage of Participants With the COVID-19 Ordinal Scale Reported
Description
Clinical status of participant at Day 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Time Frame
Study start to Day 29
Title
Change in the COVID-19 9-point Ordinal Scale
Description
Change in the Clinical status of participant at Days 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Time Frame
Study start to Days 15 and 29
Title
Change in SOFA Score
Description
Sequential Organ Failure Assessment (SOFA) score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each system gets a score from 0 (normal) to 4 (abnormal) and the sum of each score defines the final SOFA score, which 24 is the maximum score (high risk of morality) and 0 is the minimum score (low risk of mortality).
Time Frame
from baseline to Days 3, 5, 8, 11, 15, and 29
Title
Number and Percentage of Participants With Treatment-related Side Effects and Serious Adverse Events
Description
Treatment-emergent AEs are judged as related by the investigator or have a missing causality.
Time Frame
Study start to Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant or guardian health proxy must provide informed consent before any study assessment is performed.
Male or female participants aged ≥ 12 years.
Participants with coronavirus (SARS-CoV-2) infection confirmed ≤ 3 weeks prior to randomization by any test with local regulatory approval.
Participants who are intubated and receiving mechanical ventilation due to COVID-19-associated ARDS and have a PaO2/FiO2 of ≤ 300 mmHg within 6 -hours of randomization.
Participants with lung imaging showing bilateral or diffuse pulmonary infiltrates on chest x-ray or CT scan.
Exclusion Criteria:
Known history of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib.
Presence of severely impaired renal function defined by estimated creatinine clearance < 15 mL/min measured or calculated by Cockcroft-Gault equation or calculated by the updated bedside Schwartz equation. Participants must not be receiving CRRT or intermittent hemodialysis at screening.
In the opinion of the investigator, unlikely to survive for > 24 hours from randomization.
Suspected active uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19).
Currently receiving ECMO.
Participant may not be sharing a ventilator, or co-ventilating, with any other patient.
Treatment with anti-IL-6, IL-6R, IL-1RA, IL-1β, or GM-CSF antagonists, or a BTK inhibitor, within 7 days of randomization.
Treatment with a JAK inhibitor within 30 days of randomization.
Participants who are on long-term use of antirejection or immunomodulatory drugs.
Pregnant or nursing (lactating) women.
Facility Information:
Facility Name
Honor Health Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Sharp Memorial Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Teradan Clinical Trials
City
Brandon
State/Province
Florida
ZIP/Postal Code
33511
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Tampa General Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Northshore University Health System
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60678
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Indiana University Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Indiana University Health Central Indiana Cancer Centers
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46219
Country
United States
Facility Name
East Jefferson General Hospital
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Lahey Hospital & Medical Center
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
Facility Name
University of Massachusetts Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Healthpartners Cancer Care Center - Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
Mercy Research
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65804
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Rutgers Njms Clinical Research Unit
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Holy Name Medical Center
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
East Carolina University
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27858
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Kettering Cancer Care
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45429
Country
United States
Facility Name
Jefferson University Hospitals
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
West Penn Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Allegheny Health Network
City
Wexford
State/Province
Pennsylvania
ZIP/Postal Code
15090
Country
United States
Facility Name
St David'S Medical Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
University of Texas Health Science Center At Houston - McGovern Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Health Science Cente
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Wenatchee Valley Hospital and Clinics
City
Wenatchee
State/Province
Washington
ZIP/Postal Code
98801
Country
United States
Facility Name
Aurora Research Institute
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53233
Country
United States
Facility Name
Sbih City Hospital 15
City
Saint Petersburg
ZIP/Postal Code
198205
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
36226977
Citation
Rein L, Calero K, Shah R, Ojielo C, Hudock KM, Lodhi S, Sadaka F, Bellam S, Palma C, Hager DN, Daniel J, Schaub R, O'Hayer K, Theodoropoulos NM. Randomized Phase 3 Trial of Ruxolitinib for COVID-19-Associated Acute Respiratory Distress Syndrome. Crit Care Med. 2022 Dec 1;50(12):1701-1713. doi: 10.1097/CCM.0000000000005682. Epub 2022 Oct 13.
Results Reference
derived
Learn more about this trial
Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)
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